Practice Essentials

Budd-Chiari syndrome is an uncommon condition induced by thrombotic or nonthrombotic obstruction of the hepatic venous outflow and is characterized by hepatomegaly, ascites, and abdominal pain.
[49] See the image below.

Sonogram showing hepatic vein thrombus, with new vessels forming. The arrow is pointing to the thrombus.

The prognosis is poor in patients with Budd-Chiari syndrome who remain untreated, with death resulting from progressive liver failure in 3 months to 3 years from the time of the diagnosis.
[1] Following portosystemic shunting, however, the 5-year survival rate for patients with the syndrome is 38-87%. The actuarial 5-year survival rate following liver transplantation is 70%.
[2, 3, 4]

Signs and symptoms

Physical examination may reveal the following:

Jaundice

Ascites

Hepatomegaly

Splenomegaly

Ankle edema

Stasis ulcerations

Prominence of collateral veins

The clinical variants of Budd-Chiari syndrome have been described as follows
[5, 6, 7] :

Budd-Chiari syndrome should be considered separate from veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, which is characterized by toxin-induced, nonthrombotic obstruction of prehepatic veins (see the images below). (See Presentation and Workup.)

Sonogram showing hepatic vein thrombus, with new vessels forming. The arrow is pointing to the thrombus.

Pathophysiology

Occlusion of a single hepatic vein is usually silent. Overt Budd-Chiari syndrome generally requires the occlusion of at least 2 hepatic veins.
[8] Venous congestion of the liver causes hepatomegaly, which can stretch the liver capsule and be very painful. Enlargement of the caudate lobe is common because blood is shunted through it directly into the inferior vena cava (IVC).

Hepatic function can be affected to a degree, depending on the amount of stasis and the resultant hypoxia. Increased sinusoidal pressure can itself cause hepatocellular necrosis.
[49] The literature also suggests that upregulation of specific genes in chronic Budd-Chiari syndrome contributes to liver destruction through the stimulation of extracellular matrix proliferation, which contributes to liver fibrosis.

The most prominent genes involved include matrix metalloproteinase 7 and superior cervical ganglion 10 (SCG10), which are increased in expression, and thrombospondin-1, which is decreased.
[9] Overexpression of the proliferating cell nuclear antigen gene, the c -MYC oncogene, and the tumor protein p53 gene may also be etiologic factors for Budd-Chiari syndrome.
[10]

Previous

Next:

Etiology

Most patients with Budd-Chiari syndrome have an underlying thrombotic diathesis, although in approximately one third of patients, the condition is idiopathic. Thus, it may be a primary venous problem or an intra-/extrahepatic space-occupying lesion compressing/invading the venous outflow.
[49] Causes of Budd-Chiari syndrome include the following:

Congenital membranous obstructions

Type III: The inferior vena cava (IVC) cannot be filled, and collaterals have developed

Miscellaneous

Miscellaneous causes of Budd-Chiari syndrome include the following:

Alpha1-antitrypsin deficiency

Dacarbazine

Urethane

Previous

Next:

Epidemiology

Budd-Chiari syndrome is extremely rare, and the incidence is not well reported in the literature, although a study by Rajani et al found an incidence of about 1 case per million population per year in Sweden. Congenital membranous forms of Budd-Chiari syndrome are the most common cause of the disease worldwide, particularly in Asia.
[13]

A retrospective (2009-2013) nation-wide, population-based study in South Korea found a total of 424 patients with Budd-Chiari syndrome, with an average age- and sex-adjusted prevalence of 5.29 per million population.
[14] The female-to-male ratio was 1.8, the median age was 51 years, and the annual case-fatality rate was 2.8%.
[14]

The prevalence of Budd-Chiari syndrome in France appears to 4.04 per million inhabitants, with myeloproliferative neoplasms (48%), use of oral contraceptives (35%), and factor V Leiden (16%) the highest risk factors.
[52]

No data suggest that sex affects predisposition to Budd-Chiari syndrome. Nonetheless, in the United States the condition is predominantly seen in women and is associated with hematologic disorders.

Age at presentation is usually in the third or fourth decade of life, although the condition may also occur in children or elderly persons.

Previous

Next:

Prognosis

The natural history of Budd-Chiari syndrome is not well known. The following factors, however, have been associated with a good prognosis:

Younger age at diagnosis

Low Child-Pugh score

Absence of ascites or easily controlled ascites

Low serum creatinine level

In a systematic review of 79 studies, investigators found that although univariate analysis indicated bilirubin and creatinine levels as well as ascites might be significant prognostic factors, multivariate analyses did not always reveal achievement of statistical significance.
[15]

The following formula has been proposed to calculate the prognostic index for Budd-Chiari syndrome; a score of less than 5.4 is associated with a good prognosis:

The 5-year survival rate for patients with the syndrome is 38-87% following portosystemic shunting. The actuarial 5-year survival rate following liver transplantation is 70%.
[2, 3, 4] Long-term follow-up in adults has demonstrated 10-year survival rates as high as 55%.

The prognosis is poor, however, in patients with Budd-Chiari syndrome who remain untreated, with death resulting from progressive liver failure in 3 months to 3 years from the time of diagnosis.
[1]

In a University of Pennsylvania retrospective study (2008-2013) comprising 47 patients with Budd-Chiari syndrome, there were no significant differences in the treatment outcomes among those receiving anticoagulation therapy alone, transjugular intrahepatic portosystemic shunt (TIPS) placement alone, and TIPS in conjunction with anticoagulation.
[16] The investigators noted that the significant prognostic predictors for liver transplantation were age, presence of cirrhosis, and presence of chronic kidney disease.

Morbidity and mortality

Morbidity and mortality in Budd-Chiari syndrome are generally related to complications of liver failure and ascites but can also be impacted by the type of concomitant underlying disease, if any. Complications associated with Budd-Chiari syndrome include the following:

Hepatic encephalopathy

Variceal hemorrhage

Hepatorenal syndrome

Portal hypertension

Complications secondary to hypercoagulable state

Complications secondary to hepatic decompensation

Bacterial peritonitis is always of concern in the patient with ascites, especially if paracentesis is undertaken. Complications must also be considered in relation to therapies used (eg, thrombolytics). The mortality rate can be high in patients who develop fulminant hepatic failure.

Budd-Chiari syndrome can also lead to HCC (or oppositely, in some cases, develop secondary to it). In a retrospective study, Liu et al found evidence that HCC in primary Budd-Chiari syndrome is associated with blockage of the inferior vena cava and stricture of the hepatic venous outflow tract. The investigators’ results also indicated that transcatheter arterial chemoembolization (TACE) is an effective treatment for HCC in these patients, with a significant drop in alpha-fetoprotein levels after TACE treatment. The study included 246 patients with Budd-Chiari syndrome, including 14 with HCC. Ultrasonography, computed tomography (CT) scanning, magnetic resonance imaging (MRI), and angiography were used to determine the imaging characteristics in patients with HCC.
[17]

Robert Baldassano, MD Director, Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia; Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Pennsylvania School of Medicine